(4R,5S,6S,7R)-1,3-dibenzyl-5,6-dihydroxy-4,7-bis[(4-hydroxyphenyl)methyl]-1,3-diazepan-2-one | 167827-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 英文名称: (4R,5S,6S,7R)-1,3-dibenzyl-5,6-dihydroxy-4,7-bis[(4-hydroxyphenyl)methyl]-1,3-diazepan-2-one
• CAS: 167827-20-5
• 化学式: C₃₃H₃₄N₂O₅
• 分子量: 538.643
• InChiKey: RPTJRADKZYANBI-ZRTHHSRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  105
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,5S,6S,7R)-1,3-dibenzyl-5,6-dihydroxy-4,7-bis[(4-hydroxyphenyl)methyl]-1,3-diazepan-2-one 在 caesium carbonate 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  环状脲作为HIV蛋白酶抑制剂的合成和评估：P1 / P1'残基的修饰。

  摘要：

  制备了两个在P1 / P1'残基处修饰的环状脲，并评估了其对HIV蛋白酶的抑制作用和全细胞抗病毒活性。相对于先导化合物DMP323和DMP 450，化合物8b，10（3-和4-吡啶基甲基类似物）和6b（4-甲氧基类似物）显示出显着的抗病毒活性改善。

  DOI：

  10.1016/s0960-894x(98)00119-x
• 作为产物：
  描述：

  在 盐酸 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (4R,5S,6S,7R)-1,3-dibenzyl-5,6-dihydroxy-4,7-bis[(4-hydroxyphenyl)methyl]-1,3-diazepan-2-one
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n

文献信息

• Cellular accumulation of phosphonate analogs of hiv protease inhibitor compounds
  申请人：Arimilli N. Murty

  公开号：US20070010489A1

  公开（公告）日：2007-01-11

  Phosphonate substituted compounds with HIV protease inhibitory properties having use as therapeutics and for other industrial purposes are disclosed. The compositions inhibit 5 HIV protease activity and/or are useful therapeutically for the treatment of AIDS and other antiviral infections, as well as in assays for the detection of HIV protease.

  本发明揭示了具有HIV蛋白酶抑制剂性质的膦酸酯取代化合物，其具有作为治疗剂和其他工业用途的用途。该组合物抑制5型HIV蛋白酶活性和/或在治疗艾滋病和其他抗病毒感染方面具有治疗作用，以及在检测HIV蛋白酶方面的检测中有用。
• Method and compositions for identifying anti-hiv therapeutic compounds
  申请人：Birkus Gabriel

  公开号：US20070190523A1

  公开（公告）日：2007-08-16

  The invention relates to methods and compositions for identifying compounds having therapeutic activity against human immunodeficiency virus (HIV).

  本发明涉及用于鉴定具有治疗人类免疫缺陷病毒（HIV）活性的化合物的方法和组合物。
• US7649015B2
  申请人：——

  公开号：US7649015B2

  公开（公告）日：2010-01-19
• Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors
  作者：David A. Nugiel、Kim Jacobs、Tabitha Worley、Mona Patel、Robert F. Kaltenbach、Dayton T. Meyer、Prabhakar K. Jadhav、George V. De Lucca、Thomas E. Smyser、Ronald M. Klabe、Lee T. Bacheler、Marlene M. Rayner、Steven P. Seitz

  DOI：10.1021/jm960083n

  日期：1996.1.1

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.
• The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: Modifications of the P1/P1′ residues
  作者：Mona Patel、Lee T. Bacheler、Marlene M. Rayner、Beverly C. Cordova、Ronald M. Klabe、Susan Erickson-Viitanen、Steven P. Seitz

  DOI：10.1016/s0960-894x(98)00119-x

  日期：1998.4

  Two series of cyclic ureas modified at the P1/P1' residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.

  制备了两个在P1 / P1'残基处修饰的环状脲，并评估了其对HIV蛋白酶的抑制作用和全细胞抗病毒活性。相对于先导化合物DMP323和DMP 450，化合物8b，10（3-和4-吡啶基甲基类似物）和6b（4-甲氧基类似物）显示出显着的抗病毒活性改善。